Fungal microbiota sustains lasting immune activation of neutrophils and their progenitors in severe COVID-19
Gastrointestinal fungal dysbiosis is a hallmark of several diseases marked by systemic immune activation. Whether persistent pathobiont colonization during immune alterations and impaired gut barrier function has a durable impact on host immunity is unknown. We found that elevated levels of Candida...
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| Veröffentlicht in: | Nature immunology 2023-11, Vol.24 (11), p.1879-1889 |
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| creator | Kusakabe, Takato Lin, Woan-Yu Cheong, Jin-Gyu Singh, Gagandeep Ravishankar, Arjun Yeung, Stephen T. Mesko, Marissa DeCelie, Meghan Bialt Carriche, Guilhermina Zhao, Zhen Rand, Sophie Doron, Itai Putzel, Gregory G. Worgall, Stefan Cushing, Melissa Westblade, Lars Inghirami, Giorgio Parkhurst, Christopher N. Guo, Chun-Jun Schotsaert, Michael García-Sastre, Adolfo Josefowicz, Steven Z. Salvatore, Mirella Iliev, Iliyan D. |
| description | Gastrointestinal fungal dysbiosis is a hallmark of several diseases marked by systemic immune activation. Whether persistent pathobiont colonization during immune alterations and impaired gut barrier function has a durable impact on host immunity is unknown. We found that elevated levels of
Candida albicans
immunoglobulin G (IgG) antibodies marked patients with severe COVID-19 (sCOVID-19) who had intestinal
Candida
overgrowth, mycobiota dysbiosis and systemic neutrophilia. Analysis of hematopoietic stem cell progenitors in sCOVID-19 revealed transcriptional changes in antifungal immunity pathways and reprogramming of granulocyte myeloid progenitors (GMPs) for up to a year. Mice colonized with
C. albicans
patient isolates experienced increased lung neutrophilia and pulmonary NETosis during severe acute respiratory syndrome coronavirus-2 infection, which were partially resolved with antifungal treatment or by interleukin-6 receptor blockade. sCOVID-19 patients treated with tocilizumab experienced sustained reductions in
C. albicans
IgG antibodies titers and GMP transcriptional changes. These findings suggest that gut fungal pathobionts may contribute to immune activation during inflammatory diseases, offering potential mycobiota-immune therapeutic strategies for sCOVID-19 with prolonged symptoms.
Iliev et al. report that increased
Candida albicans
accumulation in the mycobiota of patients with severe COVID-19 might be a contributing factor to the immunopathology of severe COVID-19 and have long-lasting effects on the hematopoietic stem cell compartment. |
| doi_str_mv | 10.1038/s41590-023-01637-4 |
| format | Article |
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Candida albicans
immunoglobulin G (IgG) antibodies marked patients with severe COVID-19 (sCOVID-19) who had intestinal
Candida
overgrowth, mycobiota dysbiosis and systemic neutrophilia. Analysis of hematopoietic stem cell progenitors in sCOVID-19 revealed transcriptional changes in antifungal immunity pathways and reprogramming of granulocyte myeloid progenitors (GMPs) for up to a year. Mice colonized with
C. albicans
patient isolates experienced increased lung neutrophilia and pulmonary NETosis during severe acute respiratory syndrome coronavirus-2 infection, which were partially resolved with antifungal treatment or by interleukin-6 receptor blockade. sCOVID-19 patients treated with tocilizumab experienced sustained reductions in
C. albicans
IgG antibodies titers and GMP transcriptional changes. These findings suggest that gut fungal pathobionts may contribute to immune activation during inflammatory diseases, offering potential mycobiota-immune therapeutic strategies for sCOVID-19 with prolonged symptoms.
Iliev et al. report that increased
Candida albicans
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Candida albicans
immunoglobulin G (IgG) antibodies marked patients with severe COVID-19 (sCOVID-19) who had intestinal
Candida
overgrowth, mycobiota dysbiosis and systemic neutrophilia. Analysis of hematopoietic stem cell progenitors in sCOVID-19 revealed transcriptional changes in antifungal immunity pathways and reprogramming of granulocyte myeloid progenitors (GMPs) for up to a year. Mice colonized with
C. albicans
patient isolates experienced increased lung neutrophilia and pulmonary NETosis during severe acute respiratory syndrome coronavirus-2 infection, which were partially resolved with antifungal treatment or by interleukin-6 receptor blockade. sCOVID-19 patients treated with tocilizumab experienced sustained reductions in
C. albicans
IgG antibodies titers and GMP transcriptional changes. These findings suggest that gut fungal pathobionts may contribute to immune activation during inflammatory diseases, offering potential mycobiota-immune therapeutic strategies for sCOVID-19 with prolonged symptoms.
Iliev et al. report that increased
Candida albicans
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immunology</jtitle><stitle>Nat Immunol</stitle><addtitle>Nat Immunol</addtitle><date>2023-11-01</date><risdate>2023</risdate><volume>24</volume><issue>11</issue><spage>1879</spage><epage>1889</epage><pages>1879-1889</pages><issn>1529-2908</issn><eissn>1529-2916</eissn><abstract>Gastrointestinal fungal dysbiosis is a hallmark of several diseases marked by systemic immune activation. Whether persistent pathobiont colonization during immune alterations and impaired gut barrier function has a durable impact on host immunity is unknown. We found that elevated levels of
Candida albicans
immunoglobulin G (IgG) antibodies marked patients with severe COVID-19 (sCOVID-19) who had intestinal
Candida
overgrowth, mycobiota dysbiosis and systemic neutrophilia. Analysis of hematopoietic stem cell progenitors in sCOVID-19 revealed transcriptional changes in antifungal immunity pathways and reprogramming of granulocyte myeloid progenitors (GMPs) for up to a year. Mice colonized with
C. albicans
patient isolates experienced increased lung neutrophilia and pulmonary NETosis during severe acute respiratory syndrome coronavirus-2 infection, which were partially resolved with antifungal treatment or by interleukin-6 receptor blockade. sCOVID-19 patients treated with tocilizumab experienced sustained reductions in
C. albicans
IgG antibodies titers and GMP transcriptional changes. These findings suggest that gut fungal pathobionts may contribute to immune activation during inflammatory diseases, offering potential mycobiota-immune therapeutic strategies for sCOVID-19 with prolonged symptoms.
Iliev et al. report that increased
Candida albicans
accumulation in the mycobiota of patients with severe COVID-19 might be a contributing factor to the immunopathology of severe COVID-19 and have long-lasting effects on the hematopoietic stem cell compartment.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>37872315</pmid><doi>10.1038/s41590-023-01637-4</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-5566-0864</orcidid><orcidid>https://orcid.org/0000-0003-3156-3132</orcidid><orcidid>https://orcid.org/0000-0002-8296-0376</orcidid><orcidid>https://orcid.org/0000-0003-3260-2631</orcidid><orcidid>https://orcid.org/0000-0002-6551-1827</orcidid><orcidid>https://orcid.org/0000-0002-9742-5982</orcidid><orcidid>https://orcid.org/0000-0001-7453-779X</orcidid><orcidid>https://orcid.org/0000-0001-8366-4838</orcidid><orcidid>https://orcid.org/0000-0003-0884-9749</orcidid></addata></record> |
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| identifier | ISSN: 1529-2908 |
| ispartof | Nature immunology, 2023-11, Vol.24 (11), p.1879-1889 |
| issn | 1529-2908 1529-2916 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10805066 |
| source | Nature Publishing Group; MEDLINE; Alma/SFX Local Collection |
| subjects | 631/250 692/699/249 Animals Antifungal Agents Biomedical and Life Sciences Biomedicine Candida albicans Cell activation Coronaviruses COVID-19 Digestive system Dysbacteriosis Dysbiosis Gastrointestinal tract Hematopoietic stem cells Hemopoiesis Humans Immune response Immunity Immunoglobulin G Immunology Infectious Diseases Inflammatory diseases Interleukin 6 Leukocytes (granulocytic) Leukocytes (neutrophilic) Mice Mycobiome Neutrophilia Neutrophils Progenitor cells Severe acute respiratory syndrome coronavirus 2 Stem cells |
| title | Fungal microbiota sustains lasting immune activation of neutrophils and their progenitors in severe COVID-19 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-17T22%3A42%3A43IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Fungal%20microbiota%20sustains%20lasting%20immune%20activation%20of%20neutrophils%20and%20their%20progenitors%20in%20severe%20COVID-19&rft.jtitle=Nature%20immunology&rft.au=Kusakabe,%20Takato&rft.date=2023-11-01&rft.volume=24&rft.issue=11&rft.spage=1879&rft.epage=1889&rft.pages=1879-1889&rft.issn=1529-2908&rft.eissn=1529-2916&rft_id=info:doi/10.1038/s41590-023-01637-4&rft_dat=%3Cproquest_pubme%3E2881244541%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2882124704&rft_id=info:pmid/37872315&rfr_iscdi=true |